Ana B. Garcia-Delgado, Lourdes Valdes-Sanchez, Maria Jose Morillo-Sanchez, Beatriz Ponte-Zuñiga, Francisco J. Diaz-Corrales, Berta de la Cerda | Orphanet Journal of Rare Diseases | 16, 222 | 17 May 2021 | https://doi.org/10.1186/s13023-021-01843-z
Abstract
Mutations in the EYS gene are one of the major causes of autosomal recessive retinitis pigmentosa. EYS-retinopathy presents a severe clinical phenotype, and patients currently have no therapeutic options. The progress in personalised medicine and gene and cell therapies hold promise for treating this degenerative disease. However, lack of understanding and incomplete comprehension of disease's mechanism and the role of EYS in the healthy retina are critical limitations for the translation of current technical advances into real therapeutic possibilities. This review recapitulates the present knowledge about EYS-retinopathies, their clinical presentations and proposed genotype–phenotype correlations. Molecular details of the gene and the protein, mainly based on animal model data, are analysed. The proposed cellular localisation and roles of this large multi-domain protein are detailed. Future therapeutic approaches for EYS-retinopathies are discussed.
Background
Retinitis pigmentosa (RP, OMIM #26800) is the most common form of inherited retinal degeneration (IRD), with an estimated prevalence of 1 per 4,000 people. Although RP is a rare disease, it represents the primary cause of hereditary blindness in adults, affecting more than one million people worldwide [1]. EYS is a major causative gene for autosomal recessive RP (arRP) [2] in all ethnicities. EYS-retinopathy manifests early in life and produces a severe disability, currently without therapeutic options. The study of the disease's molecular mechanism has been hampered by the lack of a representative animal model for this human IRD. Information on the cellular localisation and molecular features of EYS, obtained from different vertebrate animal models, is summarised in this review to get insight into this protein's possible roles in the human retina.
Gene therapy is emerging as a safe and effective treatment for some types of RP caused by specific genes such as RPE65. Future therapeutic approaches for EYS-retinopathies are discussed based on this large gene's limitations and the current advanced therapies state-of-the-art.
References
Menghini M, Cehajic-Kapetanovic J, MacLaren RE. Monitoring progression of retinitis pigmentosa: current recommendations and recent advances. Expert Opin Orphan Drugs. 2020;8(2–3):67–78.
Abd El-Aziz MM, Barragan I, O’Driscoll CA, Goodstadt L, Prigmore E, Borrego S, et al. EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa. Nat Genet. 2008;40(11):1285–7.
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